Acid 1b Research Articles

Activation of Secondary Metabolism and Protease Activity Mechanisms in the Black Koji Mold Aspergillus luchuensis through Coculture with Animal Cells.

The activation of secondary metabolism plays a pivotal role in the discovery of novel natural products. We recently developed a coculture method involving actinomycetes and mouse macrophage-like cells to stimulate the production of bioactive compounds. A black koji mold, Aspergillus luchuensis IFM 61405, markedly enhanced the production of (3S,8R)-8-hydroxy-3-carboxy-2-methylenenonanoic acid (1a), (3S,8S)-8-hydroxy-3-carboxy-2-methylenenonanoic acid (1b), and (3S)-9-hydroxy-3-carboxy-2-methylenenonanoic acid (2) when coincubated with J774.1 mouse macrophage cells. The production of 1 and 2 increased by at least 3.5-fold and 2.7-fold, respectively, compared to monoculture after 7 days. A mechanistic investigation revealed that a protease from strain IFM 61405 plays a key role in enhancing the production of 1 and 2. This enhancement was not replicated in A. niger IFM 59706, a nonkoji mold, despite the presence of biosynthetic genes for 1 and 2 in A. niger IFM 59706. Furthermore, the addition of protease inhibitors suppressed the production of 1 and 2, suggesting that proteins secreted from animal cells, likely degraded by proteases secreted by strain IFM 61405, serve as precursors for 1 and 2. The results show that the strategy of coculturing koji mold with animal cells has the potential to enhance the production of natural products.

Design, Synthesis, and Evaluation of Triazoline Schiff Bases as Potential Antibacterial Agents Against Methicillin-Resistant Staphylococcus aureus (MRSA): A Comprehensive Computational and Experimental Study

In this study, a series of novel triazoline Schiff bases are designed and synthesized on a triazole-based AADHR_1 hypothesis pharmacophore model tailored to meet structural requirements for antibacterial activity. FT-IR, 1H-NMR, and 13C-NMR spectroscopy techniques confirmed molecular structures. Assessment of ADMET properties utilizing the pkCSM online tool unveiled encouraging pharmacokinetic profiles. Detailed Density Functional Theory (DFT) calculations showed significant electronic properties, delineating certain compounds as potent electron donors or acceptors. Docking studies unveil that, the compound 1-((1-(p-tolyl)piperidin-4-yl)methyl)-1H-1,2,3-triazole-4-carboxylic acid (2b) binded into the active site of the Penicillin-binding protein (PBP2a) of Methicillin-resistant Staphylococcus aureus (MRSA) with the docking score of -8.0 kcal/mol. Molecular dynamics simulations further corroborated the stability of the protein-ligand complex, emphasizing the compound 2b is enduring interaction at the MRSA protein's active site. Antibacterial assays against MRSA showed selective compounds exhibiting minimum inhibitory concentrations (MICs) of 20µg/mL and Zone of inhibition up to 14mm, highlighting their potential as effective antimicrobial agents against antibiotic-resistant bacteria. These findings collectively suggest the promising therapeutic prospects of the synthesized triazoline Schiff bases in combatting MRSA infections.

Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth.

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.

Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

Study of the Molecular Architectures of 2-(4-Chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic Acid Using Their Vibrational Spectra, Quantum Chemical Calculations and Molecular Docking with MMP-2 Receptor.

1,2,3-triazole skeleton is a valuable building block for the discovery of new promising anticancer agents. In the present work, the molecular structure of the synthesized anticancer drug 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid (1b) and its anionic form (2b) was characterized by means of the B3LYP, M06-2X and MP2 quantum chemical methods, optimizing their monomer, cyclic dimer and stacking forms using the Gaussian16 program package. The molecular structure was found to be slightly out of plane. The good agreement between the IR and Raman bands experimentally observed in the solid state with those calculated theoretically confirms the synthesized structures. All of the bands were accurately assigned according to functional calculations (DFT) in the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE). Therefore, the effect of the substituents on the triazole ring and the effect of the chlorine atom on the molecular structure and on the vibrational spectra were evaluated through comparison with its non-substituted form. Through molecular docking calculations, it was evaluated as to how molecule 1b interacts with few amino acids of the MMP-2 metalloproteinase receptor, using Sybyl-X 2.0 software. Thus, the relevance of triazole scaffolds in established hydrogen bond-type interactions was demonstrated.

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues.

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 μM, as compared to CA-4 (IC50 = 1.27 ± 09 μM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against β-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

Serendipitous discovery of a regioselective synthesis of novel benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters, 3-benzoyloxy-3-(phenylsulfanyl)-β-lactams and their antimicrobial evaluation

The regioselective benzoyloxylation process involves stirring a mixture of phenyl/benzyl-sulfanyl/selenylethanoate 1a-c with appropriate oxidant [benzoyl peroxide (BPO) 2a/ m-chloroperbenzoic acid (m-CPBA) 2b /bis(p-methoxybenzoyl peroxide) (BPM-BPO) 2c] under catalysis of hydrated copper acetate in toluene at 60 °C/RT. Regioselective C–H functionalization of esters 1a-c leads to benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters 3a-g in good to excellent yields (80–95%). Variably substituted trans-3-phenylsulfanyl-β-lactams 4 employed for C3-H functionalization with BPO 2a generates diastereoisomeric mixture of trans- and cis-3-benzoyloxy-3-(phenylsulfanyl)-β-lactams 5 and 6 as major and minor isomers after efficient column chromatographic purification. The structural confirmation was done using IR, 1H NMR, 13C NMR, DEPT-90 NMR spectroscopic analysis and CHNS elemental analysis. In vitro antibacterial and antifungal evaluations on bisesters suggest benzylselenyl-bisester 3c as potent antimicrobial agent. Out of trans- and cis-3-benzoyloxy-β-lactams 5a and 6a, the trans isomer 5a was active against all microbial strains whereas the cis isomer 6a was completely inactive.

Kinetic studies of copper-catalyzed homocoupling reactions of arylboronic acids in aqueous micellar media

The kinetic studies for copper-catalyzed homocoupling phenylboronic acids (1a-d) have been successfully carried out in an aqueous micellar medium under environmentally benign conditions (water as a solvent, micelle to help solubilize hydrophobic adducts) in this study cetyl trimethyl ammonium bromide (CTAB ) is used as surfactant to produce micelle. Using different copper salts and copper complexes as catalysts under benign to mild conditions at a temperature range (40-65˚C, under air) without the addition of any additives (base, oxidant, and ligands). The reactions were followed using a UV-Vis spectrophotometer and the absorbances were measured at maximum wavelengths for the biphenyl production of each five selected (1a-d). The observed rate constants (kobs) were calculated using a pseudo-first-order equation and unsubstituted 1a was selected for optimization processes. The experimental results showed good to excellent curve fit (R2=0.9967-0.9998) to the pseudo-first-order equation and origin software was used for this purpose. Among all copper catalysts, the observed rate constant (kobs) for cupric acetate (Cu(OAc)2)is much higher than others, (kobs=0.1605 min-1), while CuCl2.2H2O has a minimum observed rate constant, kobs=0.0216min-1. The two copper complexes [Cu(4-mba)2(tmeda)], and [Cu(3-mba)2(H2O)2(tmeda)] require a mild condition (85˚C) which is higher than other copper catalysts when 1a is used as reactant the value of kobs is (0.0176, 0.0343 min-1) respectively, while using p-tolylboronic acid (1b) as reactant the value of kobs is (0.0173, 0.0147 min-1) respectively.

Chitosan-carbamoylcarboxylic acid grafted polymers for removal of metal ions in wastewater

Water contamination by heavy metals is reported all over the world and requires strategic solutions to minimize its environmental impact. In this work, new materials based on chitosan (Q) were grafted with new mono carbamoylcarboxylic acids (mCCA) 1a and 1b were evaluated in the simultaneous removal of six metal ions by coagulation-flocculation process. The physicochemical properties and the interaction of carbamoylcarboxylic acid (CCA)-chitosans Q-1a and Q-1b, chitosan, 1a and 1b with metal ions were analyzed by zeta potential (ζ). CCA-chitosan Q-1a-5 shows significant removal of Cu2+ (99.8 %), Ni2+ (73.1 %) and Zn2+ (67.0 %) and optimal removal dose (ORD) of 20.0 mg/g of M2+, as well as Q-1b-10 performs the removal of Pb2+ (98.8 %), Cu2+ (99.1 %) and Ni2+ (81.1 %) with an ORD of 23.0 mg/g of M2+. The global metal ions removal is 81.2 % with Q-1a-5 and 79.3 % for Q-1b-10, highly superior than chitosan (42.3 % and ORD 34.3 mg/g of M2+). CCA-chitosan Q-1a-5 and Q-1b-10 show an improved clarification kinetics (18.3 and 56.8 T%/h, respectively), sedimentation ratio (10.6 and 48.5 mm/h, respectively) and a Turbiscan Stability Index (TSI) value (40.2 and 80.2, respectively) and the metal ions removal is associate to a sedimentation, flocculation and coalescence phenomena, displaying the best characteristics for the wastewater treatment containing different metal ions.

Synthesis and Spectroscopic Characterization of Selected Phenothiazines and Phenazines Rationalized Based on DFT Calculation.

Two unique structures were isolated from the phosphorylation reaction of 10H-phenothiazine. The 5,5-dimethyl-2-(10H-phenothiazin-10-yl)-1,3,2-dioxaphosphinane 2-oxide (2a) illustrates the product of N-phosphorylation of phenothiazine. Moreover, a potential product of 2a instability, a thiophosphoric acid 2b, was successfully isolated and structurally characterized. Molecule 2a, similarly to sulfoxide derivative 3, possesses interesting phosphorescence properties due to the presence of d-pπ bonds. The X-ray, NMR, and DFT computational studies indicate that compound 2a exhibits an anomeric effect. Additionally, the syntheses of selected symmetrical and unsymmetrical pyridine-embedded phenazines were elaborated. To compare the influence of phosphorus and sulfur atoms on the structural characteristics of 10H-phenothiazine derivatives, the high-quality crystals of (4a,12a-dihydro-12H-benzo[5,6][1,4]thiazino[2,3-b]quinoxalin-12-yl)(phenyl)methanone (1) and selected phenazines 5,12-diisopropyl-3,10-dimethyldipyrido[3,2-a:3',2'-h]phenazine (5) and 5-isopropyl-N,N,3-trimethylpyrido[3,2-a]phenazin-10-amine (6a) were obtained. The structures of molecules 1, 2a, 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxide (2b), 3,7-dinitro-10H-phenothiazine 5-oxide (3), 5 and 6a were determined by single-crystal X-ray diffraction measurements.

Assessment of the α-glucosidase and α-amylase inhibitory potential of Paliurus spina-christi Mill. and its terpenic compounds

Type II diabetes mellitus is a common disease in the world and characterized by hyperglycemia. Prevention of diabetes by reducing hyperglycemia depends on the inhibition of α-amylase and α-glucosidase enzymes. In this study, the antidiabetic profiles of the Paliurus spina-christi Mill. fruit were investigated. The fruit of this species is used as an antidiabetic in folk medicine in Turkey. α-amylase and α-glucosidase inhibitory effect studies were conducted to prove this effect. The n-hexane sub-extract of the methanolic fruit extract (IC50 = 445.7 ± 8.5 µg/mL) showed greater inhibitory activity against α-glucosidase than acarbose (IC50 = 4212.6 ± 130.0 µg/mL), in contrast to its slight/no inhibitory effect on α-amylase. The phytochemical investigation of the n-hexane sub-extract of the P. spina-christi fruit led to the isolation of three triterpenes, namely betulin (1a), betulinic acid (1b), and lupeol (2), and a sterol (β-sitosterol) (3). The structures of compounds 1-3 were further analyzed using extensive 1D- and 2D-NMR, and the results were compared with literature. Betulin (1a), betulinic acid (1b), and lupeol (2) are reported from this species for the first time. All the isolated compounds, especially betulin (1a) and betulinic acid (1b) mixture (IC50 = 248 ± 12 µM) showed higher α-glucosidase inhibitory activity than acarbose (IC50 = 6561 ± 207 µM). As extracts, the compounds were also found to be ineffective against α-amylase. Graphical abstract

Photocatalytic activity of graphene oxide/zinc oxide nanocomposite derived from rice husk for the degradation of phenanthrene under ultraviolet-visible light

Environmental concerns have arisen due to the persistent nature and carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). This study used the doping approach to successfully develop a nanocomposite photocatalyst based on graphene oxide (GO) and zinc oxide (ZnO). The nanocomposites were investigated by Fourier transform infrared (FTIR) spectroscopy, UV–Visible diffuse reflectance spectroscopy (UV–Vis DRS), x-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive x-ray (EDX), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), and Raman spectroscopy. GO/ZnO nanocomposite showed excellent ability to degrade 25 ppm of phenanthrene (86.06%) in 120 min under UV–Visible light exposure followed by photolysis (no photocatalyst) (15.56%), GO/ZnO without stirring (40.28%), GO/ZnO in the dark with stirring (47.40%), and commercial ZnO (62.84%). This is due to the largest surface area, which was enhanced by the doping of GO in commercial ZnO. Phenanthrene photodegradation by GO/ZnO nanocomposite followed first-order kinetics with a rate constant of 0.0375 min−1. The smaller byproducts like (Z)-3-hydroxy acrylic acid (1b; m/z = 88) and (Z)-4-oxobut-2-enoic acid (1c; m/z = 100) identified in GC–MS, clearly demonstrated e− excitement from encapsulated nanocatalyst followed by OH (active species) based oxidation of phenanthrene. Consequently, the GO/ZnO nanocomposite could be a versatile photocatalyst for the photodegradation of phenanthrene in wastewater treatment.

Self-Assembled Lanthanide Antenna Glutathione Sensor for the Study of Immune Cells.

The small molecule 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-carboxylic acid (2b) behaves as a reactive non-fluorescent Michael acceptor, which after reaction with thiols becomes fluorescent, and an efficient Eu3+ antenna, after self-assembling with this cation in water. This behavior makes 2b a highly selective GSH biosensor, which has demonstrated high potential for studies in murine and human cells of the immune system (CD4+ T, CD8+ T, and B cells) using flow cytometry. GSH can be monitored by the fluorescence of the product of addition to 2b (445 nm) or by the luminescence of Eu3+ (592 nm). 2b was able to capture baseline differences in GSH intracellular levels among murine and human CD4+ T, CD8+ T, and B cells. We also successfully used 2b to monitor intracellular changes in GSH associated with the metabolic variations governing the induction of CD4+ naïve T cells into regulatory T cells (TREG).

3-Aryl-2-azidopropanoic acids in cycloaddition reactions

3-Aryl-2-azidopropanoic acids and their derivatives were studied in the [3+2] and [2+2] cycloaddition reactions. New heterocyclic scaffolds of 3-aryl-2-(1 H -1,2,3-triazol-1-yl)propanoic acids, [1,2,3]triazolo[1,5-a]pyrazin-6(7 H )-one and [1,2,3]triazolo[1,5-a]pyrazine-4,6(5 H ,7 H )-dione were obtained. α-Azidoacids and their derivatives are convenient precursors in the synthesis of drug-like compounds. The azido group can be used as a protected amino group or a precursor of the 1,2,3-triazole ring as a bioisostere to amide moiety. α-Azidoacids are synthetically available and can be easily obtained in diazotransfer reactions from the corresponding α-aminoacids or during the anionic Meerwein arylation of acrylates. In view of this, we decided to investigate them in 1,3-dipolar cycloaddition reactions in order to obtain new compounds for the study of their biological properties. 3-Aryl-2-azidopropanoic acids were investigated in 1,3-dipolar cycloaddition reactions to alkynes. The interaction of acids 1a,b with diethyl ester acetylenedicarboxylic acid 2 under Huisgen cycloaddition (metal free) resulted in the formation of 3-aryl-2-triazolylpropanoic acids 3a,b with good yields. The presence of compounds 3 of carboxyl and ester groups makes them convenient precursors for further heterocyclizations. On the example of 3-aryl-2-triazolylpropanoic acid 3b we have shown the possibility of obtaining [1,2,3]triazolo[1,5- a ] pyrazine rings. The acid 3b was converted by the action of oxalyl chloride to the corresponding acid chloride 4b , the latter in the reaction with isobutylamine under heating led to the formation of a bicyclic derivative 5b . Another synthetic approach to obtaining [1,2,3]triazolo[1,5- a ]pyrazines is the intramolecular cyclization of propargylamides of 2-azidoacids. To implement this approach, we obtained from 3-aryl-2-azidopropanoic acids 1c-f the corresponding propargyl amides 7c-f through intermediate chlorides 6c-f . Reflux of amides 7d,e in toluene for 24 h allowed to obtain the target [1,2,3]triazolo[1,5- a ]pyrazines 8d,e with low yields. We investigated 3-aryl-2-azidopropanoic acid chlorides 6c,f under the conditions of the [2+2]cycloaddition reaction with Schiff bases. However, in contrast to unsubstituted azidoacetic acid chloride, the interaction of acid chlorides 6c , f with Schiff bases 9a,b in the presence of triethylamine as a base at –20 o C did not lead to the formation of azetidinones 10 . The main reaction products were amides 11a,b . Thus, 3-aryl-2-azidopropanoic acids and their derivatives in cycloaddition reactions were investigated. A number of new functionalized 1,2,3-triazole and [1,2,3]triazolo[1,5- a ]pyrazine derivatives were synthesized. The obtained substances can be used for further modifications, and are of considerable interest for medical and pharmaceutical chemistry. Keywords: 3-aryl-2-azidopropanoic acids, alkynes, 1,3-dipolar cycloaddition, 1,2,3-triazoles, [1,2,3]triazolo[1,5- a ]pyrazines.

Utilization of cyanopyridine in design and synthesis of first-in-class anticancer dual acting PIM-1 kinase/HDAC inhibitors

Herein, we report design and synthesis of twenty-one dual PIM-1/HDAC inhibitors utilizing 3-cyanopyridines as a novel cap moiety linked with aliphatic /aromatic linker bearing carboxylic acid 3a-g, hydroxamic acid 4a-g or 2-aminoanilide moieties 5a-g as zinc-binding group. Most of the target hybrids revealed promising growth inhibition according to one dose NCI protocol against 60 cancer cell lines. Meanwhile, hydroxamic acids 4b, 4d and 4e displayed strong and broad-spectrum activity against nine tumor subpanels tested (GI50 0.176–8.87 μM); 4d displayed strong antiproliferative activity with GI50 ≤ 3 μM against different cancer cell lines (GI50 range from 0.325 to 2.9 μM). Furthermore, 4a, 4d-4g and 5f manifested a high inhibitory activity against HDACs 1 and 6 isozymes; 4g, displayed potent HDAC 1 and 6 inhibitory activity (45.01 ± 2.1 and 19.78 ± 1.1 nM) more than the reference SAHA (51.54 ± 2.4 and 21.38 ± 1.2 nM, respectively), while 4f was more potent (30.09 ± 1.4 nM) than SAHA against HDAC 1 and less potent (30.29 ± 1.7 nM) than SAHA against HDAC 6. Hybrids 4b, 4d, 4e and 4f exhibited potent PIM-1 inhibitory activity; 4d showed comparable activity to quercetin (IC50 of 343.87 ± 16.6 and 353.76 ± 17.1 nM, respectively); it exhibited pre G1 apoptosis and arrest cell cycle at G2/M phase. Moreover, it revealed good binding into pocket of HDACs 1,6 and PIM-1 kinase enzymes with good correlation with biological results. Moreover, 4b, 4d and 4e had reasonable drug-likeness properties according to Lipinski’s rule. However, multitarget inhibitor of PIM-1/HDAC is a promising strategy in anticancer drug discovery; the most potent hybrids require further in vivo and clinical investigations.

Peanut meal extract fermented with Bacillus natto attenuates physiological and behavioral deficits in a D-galactose-induced aging rat model.

Our previous studies have shown that the nutritional properties of peanut meal after fermentation are markedly improved. In this study, in order to facilitate the further utilization of peanut meal, we investigated the effects of its fermentation extract by Bacillus natto (FE) on cognitive ability, antioxidant activity of brain, and protein expression of hippocampus of aging rats induced by D-galactose. Seventy-two female SD rats aged 4-5 months were randomly divided into six groups: normal control group (N), aging model group (M), FE low-dose group (FL), FE medium-dose group (FM), FE high-dose group (FH) and vitamin E positive control group (Y). Morris water maze (MWM) test was performed to evaluate their effects on learning and memory ability in aging rats. SOD activity and malondialdehyde (MDA) content of brain, HE staining and the expression of γ-aminobutyric acid receptor 1 (GABABR1) and N-methyl-D-aspartic acid 2B receptor (NMDAR2B) in the hippocampus of rats were measured. The results show that FE supplementation can effectively alleviate the decrease of thymus index induced by aging, decrease the escape latency of MWM by 66.06%, brain MDA by 28.04%, hippocampus GABABR1 expression by 7.98%, and increase brain SOD by 63.54% in aging model rats. This study provides evidence for its anti-aging effects and is a research basis for potential nutritional benefits of underutilized food by-products.

Cussonia arborea Hochst (Araliaceae): Ethnobotany, Pharmacology and Phytochemistry

Background: C. arborea belonging to Araliaceae family is used traditionally to cure many alien diseases including gonorrhoeae infection, diarrhea, malaria, and diabetes mellitus. The plant has been examined on the basis of scientific in vitro and in vivo evaluations possessing the major pharmacological activities including antimicrobial, antibacterial, antihyperglycemic, antiplasmodial and anticancer properties.
 Aim of the study: In the present paper, we reported the isolation and characterization of secondary metabolites from the methanol extract of the stem bark of Cussonia arborea Hochst after a short review of the traditional and pharmacological studies done on this important medicinal plant.
 Materials and methods: MeOH extract of stem bark of C. arborea was suspended in water and successively extracted with EtOAc and n-BuOH. The EtOAc extract (18 g) was subjected to repeated column chromatography to yield seven (1-7) compounds. Their structures were determined by means of NMR, and published data.
 Results: The isolated compounds were identified as: protocatechuic acid (1), mixture of 3,23-dihydroxyolean-12-en-28-oic acid (2a) and 3,23-dihydroxyurs-12-en-28-oic acid (2b) in ratio 5/4, 3-O-β-D-xylopyranosylolean-12-en-28-oic acid (3), 3-O-α-L-arabinopyranosylolean-12-en-28-oic acid (4), β-resorcylic acid (5), mixture of 3-O-β-D-glucopyranosyl-23-hydroxyolean-12-en-28-oic acid (6a) and 3-O-β-D-glucopyranosyl-23-hydroxyurs-12-en-28-oic acid (6b) in ration 4/1, 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-3β-hydroxyolean-12-en-28-oic acid (7). Compounds 3, 4, 5, 7, 2b and 6b are herein reported for the first time in this plant

Antibacterial constituents from the roots, stem bark and leaves of Manilkara obovata (Sabine & G. Don) J. H. Hemsl. (Sapotaceae)

• Obovacoumaric acid and obovatol were isolated from the methanolic extracts of Manilkara obovata . • A new ethylcanophyllate was obtained by esterification of canophyllic acid. • The structures were elucidated by NMR and single crystal X-ray crystallography. • Antibacterial effects of the methanolic extracts of Manilkara obovata . The investigation of the methanolic extracts of the roots, stem bark and leaves of Manilkara obovata (Sabine & G. Don) J. H. Hemsl. (Sapotaceae), synonym Manilkara argentea Pierre ex Dubard, has led to the isolation and characterization of a new 4-phenylcoumarin derivative, in form of a racemic mixture of obovacoumaric acid ( 1a ) and the previously reported callophyllic acid ( 1b ) as well as a new taraxerane type triterpene named obovatol ( 2 ), alongside twenty-five known compounds. In addition, ethylcanophyllate ( 3a ), obtained by esterification of canophyllic acid ( 3 ) is reported here for the first time. The structures of compounds were determined by comprehensive spectroscopic analyses of their 1D and 2D NMR, EI/ESI-MS and single crystal X-ray diffraction (SC-XRD) analysis for 1a and 1b , accompanied by comparison with reported records. In addition, the antibacterial activity of crude extracts, fractions and some of the isolated compounds including the hemi-synthesized ethylcanophyllate ( 3a ) was determined against Salmonella typhi , Staphylococcus aureus ATCC4330, Enterobacter cloacae , Pseudomonas aeruginosa HM801, Streptococcus pneumoniae ATCC491619 and Escherichia coli ATCC25322 applying the broth microdilution method. While the methanolic stem bark extract showed good to significant activity against all bacterial test strains with MICs between 7.8 and 62.5 μg/mL, its fractions A and B were less active, indicating synergistic effects. This effect was also observed for the methanolic root extract, which gave a significant MIC against Staphylococcus aureus ATCC4330 with MIC < 3.9 μg/mL, but only MICs of 31.2 and 7.8 μg/mL for its fractions D and E. Likewise, though fractions F 3 and F 4 of the methanolic leaf extract displayed good MICs of 31.2 and 15.6 μg/mL, respectively, against Staphylococcus aureus ATCC4330, tested compounds were not stronger active. Interestingly, the hemi-synthesized ethylcanophyllate ( 3a ) based on the completely antibacterial inactive canophyllic acid ( 3 ) displayed a good MIC of 15.6 μg/mL against Staphylococcus aureus ATCC4330, pointing here to a dominant role of the ester function in compound 3a in the structure-activity relationship.

Absolute Configuration Sensing of Chiral Aryl- and Aryloxy-Propionic Acids by Biphenyl Chiroptical Probes

The absolute configuration of chiral 2-aryl and 2-aryloxy propionic acids, which are among the most common chiral environmental pollutants, has been readily and reliably established by either electronic circular dichroism spectroscopy or optical rotation measurements employing suitably designed 4,4′-disubstituted biphenyl probes. In fact, the 4,4′-biphenyl substitution gives rise to a red shift of the diagnostic electronic circular dichroism signal of the biphenyl A band employed for the configuration assignment, removing its overlap with other interfering dichroic bands and allowing its clear sign identification. The largest A band red shift, and thus the most reliable results, are obtained by employing as a probe the 4,4′-dinitro substituted biphenylazepine 3c. The method was applied to the absolute configuration assignment of 2-arylpropionic acids ibuprofen (1a), naproxen (1b), ketoprofen (1c) and flurbiprofen (1d), as well as to the 2-aryloxypropionic acids 2-phenoxypropionic acid (2a) and 2-naphthoxypropionic acid (2b). This approach, allowing us to reveal the sample’s absolute configuration by simple optical rotation measurements, is potentially applicable to online analyses of both the enantiomeric composition and absolute configuration of these chiral pollutants.

Rhodanine-3-acetamide derivatives as aldose and aldehyde reductase inhibitors to treat diabetic complications: synthesis, biological evaluation, molecular docking and simulation studies

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a–g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a–g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall, the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2. The binding site analysis of potent compounds revealed similar interactions as were found by cognate ligands within the active sites of enzymes.